Dr Fayyaz Chaudhri

• Maryport Health Services

• GPwSI

Solar (actinic) Keratosis

• Background of solar elastosis

• multiple flat or thickened

• scaly or warty

• skin coloured or reddened lesions.

• cutaneous horn

www. dermnetnz.org

Treatment Options• Cryotherapy

• Curettage & cautery

• Excision

• 5-Fluorouracil cream

• Imiquimod

• Photodynamic therapy

• Diclofenac gel

5-FU (efudix)

• useful when there are many lesions on the face.

• applied once or twice daily for two to four weeks.

• Expect inflammation - red, raw and uncomfortable.

• Good end results

5-fluorouracil is a structural analogue of Thymine and Uracil with the 5-methyl group being replaced by fluorine.

Its activity can be explained by two mechanism:

Thymine

F

5-fluorouracilUracil

5-Fluorouracil : Mechanism of Action

UK/EFU/12/0007

Ref : Goette DK, J Am Acad Dermatol 1981;4(6):633-649

i) Metabolite competition 5-FU competes with normal metabolites for access to enzyme active sites and is eventually incorporated

into the host cell RNA molecules. These become ineffective molecules for protein synthesis 1,2

ii) Enzyme inhibition The 5-FU metabolite (5F-deoxyuridine monophosphate)

blocks the essential enzyme thymidylate synthetase thus preventing DNA synthesis 1,2

5-Fluorouracil : Mechanism of Action

UK/EFU/12/0007

Ref : Goette DK, J Am Acad Dermatol 1981;4(6):633-649

F

5-FU

Ineffective mRNA

F

5-Fluorouracil : Mechanism of Action

Triplet does not code for an

amino acid t-RNA

UK/EFU/12/0007

DNA replicationMaking new copies for dividing cells

F

5-fluorouracil metabolite inhibits thymidylate

synthetase

x

Enzyme inhibition Reduced DNA production

5-Fluorouracil : Mechanism of Action

ii) Enzyme inhibition

UK/EFU/12/0007

2 weeks after Efudix treatment

Therapeutic response depends on severity of disease

• Phase 1 - early, mild inflammation transformed cells die by necrosis

leading to ....• Phase 2 - Severe inflammation

• Phase 3 – lesion destruction and macrophage clearance

• Phase 4 – Scabbing, new tissue production and healing process.

Ref: Litwin MS, Ryan RF Reed Ej et al. J Surg Oncol 1971;3:351-65

5-Fluorouracil : Mechanism of Action

UK/EFU/12/0007

Excessive reaction

Imiquimod

• immune response modifier

• 2-3 times weekly for 4-12 weeks.

• inflammatory reaction,

• results are variable, but generally excellent.

AK treated with IMIQUIMOD

4 WEEKS AFTER TREATMENT

Intraepidermal SCC – Bowens

scc